Project description:While microbiome and pregnancy are known to alter drug disposition, the interplay of the two physiological factors to impact expression and/or activity of drug processing genes (DPGs) has yet to be elucidated. This study aimed to investigate the effects of microbiome on host hepatic DPGs during pregnancy using conventional (CV) and germ-free (GF) mice. Four groups of female mice were used, namely CV non-pregnant (CVNP), GF non-pregnant (GFNP), CV pregnant (CVP), and GF pregnant (GFP) mice. Pregnant mice examined were on gestation day 15. Transcriptomic and targeted proteomics of hepatic DPGs were profiled using a multi-omics approach. Plasma bile acid and steroid hormone levels were quantified using LC-MS/MS. Cyp3a activities were measured by mouse liver microsome incubations. While the overall trend in pregnancy-induced changes in the expression or activity of hepatic DPGs in CV and GF mice was similar, significant differences in the magnitude of changes were observed. For certain genes, we noticed opposite effects of pregnancy on mRNA and protein expression of DPGs in both CV and GF mice. For instance, the mRNA levels of Cyp3a11, the murine homolog of human CYP3A4, were decreased by 1.7-fold and 3.3-fold by pregnancy in CV and GF mice, respectively. However, the protein levels of Cyp3a11 were increased similarly ~2-fold by pregnancy in both CV and GF mice. Yet, microsome incubations revealed a marked induction of Cyp3a activity by pregnancy that was >5-fold greater in CV mice than that in GF mice. Plasma bile acid and steroid hormone levels were also significantly altered by microbiome and pregnancy, respectively, which may contribute to the differential effects of pregnancy in CV and GF mice. This is the first study to show that microbiome can alter hepatic DPGs in pregnancy.
Project description:Objectives: Arterial hypertension (AH) influences salivary gland physiology and oral health, being associated with a higher incidence of periodontal disease in pregnant women. Evidence points to a bidirectional relationship between the oral microbiota and blood pressure regulation. Therefore, this study aimed to characterize the oral health of pregnant women and AH-associated changes in the salivary proteome and microbiome during pregnancy and postpartum. Design: Ten healthy women and ten women with AH were enrolled. Saliva was collected during pregnancy and six months postpartum. The salivary proteome was characterized by shotgun label-free mass spectrometry analysis. Specific proteins were validated through parallel reaction monitoring (PRM). The oral microbiota was characterized via 16S rRNA gene amplicon sequencing (V4 region). The periodontal health and the caries history was assessed during pregnancy. Results: Pregnant women with AH had lower junction plakoglobin (JUP)- and desmoplakin (DSP)-specific peptide levels than healthy women, confirmed by the PRM approach. The levels of these proteins correlated negatively with periodontal health indexes, which were higher in pregnant women with AH. In AH, nitrate-reducing microorganisms had lower abundance, correlating positively with JUP and DSP-specific peptides. Conclusions: The salivary proteome and microbiota are shaped by AH during and after pregnancy. Further research is required to understand the underlying mechanisms impairing oral health in AH. Data acquisition has been supported by EPIC-XS, project number 393, funded by the Horizon 2020 program of the European Union and the National Institute for Neurological Research (Programme EXCELES, ID Project No. LX22NPO5107) and the MEYS/EU project OP JAK-MULTIOMICS_CZ - Multi-omics platform for the search for biological correlates of diseases and the development of new diagnostic, preventive and therapeutic procedures (CZ.02.01.01/00/23_020/0008540).
2025-12-03 | PXD071471 | Pride
Project description:Metabarcoding Analysis of Oral Microbiome during pregnancy
Project description:The objectives of this study were to establish a microbiome profile for oral epithelial dysplasia using archival lesion swab samples to characterize the community variations and the functional potential of the microbiome using 16S rRNA gene sequencing
Project description:Clinical treatment protocols for infertility with in vitro fertilization-embryo transfer (IVF-ET) provide a unique opportunity to assess the human vaginal microbiome in defined hormonal milieu. Herein, we have investigated the association of circulating ovarian-derived estradiol (E2) and progesterone (P4) concentrations to the vaginal microbiome. Thirty IVF-ET patients were enrolled in this study, after informed consent. Blood was drawn at four time points during the IVF-ET procedure. In addition, if a pregnancy resulted, blood was drawn at 4-to-6 weeks of gestation. The serum concentrations of E2 and P4 were measured. Vaginal swabs were obtained in different hormonal milieu. Two independent genome-based technologies (and the second assayed in two different ways) were employed to identify the vaginal microbes. The vaginal microbiome underwent a transition with a decrease in E2 (and/or a decrease in P4). Novel bacteria were found in the vagina of 33% of the women undergoing IVF-ET. Our approach has enabled the discovery of novel, previously unidentified bacterial species in the human vagina in different hormonal milieu. While the relationship of hormone concentration and vaginal microbes was found to be complex, the data support a shift in the microbiome of the human vagina during IVF-ET therapy using standard protocols. The data also set the foundation for further studies examining correlations between IVF-ET outcome and the vaginal microbiome within a larger study population.